Pacemaker and defibrillator devices use electrical impulses to regulate beating of the heart. Current implantable artificial pacemakers and defibrillators rely on a programmable electronic device and wired electrodes to electrically stimulate and synchronize beating of the myocardium (pacemaker) or to correct cardiac arrhythmia (defibrillator). However, these implantable devices are unresponsive to autonomic heart rate modulation, require invasive surgical implantation and replacement every 5-10 years, are susceptible to temporary malfunction in the presence of magnets, e.g., metal detectors or MRI machines, or environmental noise, and increase the patient's inflammatory response and risk of infection. They have a limited battery life and their long-term use has been associated with permanent cardiac tissue damage. In addition, these electronic devices are often unsuitable for pediatric patients (see, e.g., emedicine.medscape.com/article/780825-overview).
Furthermore, implantable electrical cardiac defibrillators function by delivering a large, brief electric shock to reset a tachycardic/fibrillating heart and restore normal beating. Like pacemakers, the defibrillators must be implanted surgically and are prone to mechanical failure. A major complaint of patients with implanted defibrillators is the extreme pain from the electric shock produced by the devices.
Biological pacemakers are one alternative to artificial electrical pacing therapy. Biological pacemakers are responsive to autonomic modulation, require no external power source or replacement, present minimal inflammatory response, can be permanent, and can be autologous. Attempts at restoring cardiac automaticity with biologics have recently focused on two main approaches: gene therapy and cell transplantation (reviewed in M R Rosen et al., Anat. Rec. Part A 280A: 1046-1052, 2004). Gene therapy approaches introduce genes, such as the pacemaker gene, HCN2, directly into myocardial cells to restore or enhance automaticity. For example, adenovirus carrying an HCN2 construct has been injected into the left ventricular bundle branch system of canine hearts. Upon vagal stimulation, transgenic hearts demonstrated a more rapid heart rate than control hearts. Cell transplantation approaches involve transplanting isolated spontaneously active or genetically-engineered cells directly into the myocardium. For example, adult mesenchymal stem cells have been transformed with HCN2. The transformed stem cells were injected into the left ventricular anterior wall of a canine heart and were capable of stimulating heart rhythms (M R Rosen et al., Anat. Rec. Part A 280A: 1046-1052, 2004).
These short-term studies demonstrate the potential of biological pacemakers. Biological defibrillators have not, as yet, been explored. However, for both technologies, miniaturized systems and a minimally invasive means to access and regulate the cellular devices would facilitate and optimize control and repair of cardiac function in patients. Thus, there is a need in the art for biological pacemakers and/or defibrillators which are less invasive and more effective in regulating beating of the heart.